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Record W4361191279 · doi:10.1128/aac.01600-22

The Natural Stilbenoid (–)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9

2023· article· en· W4361191279 on OpenAlexafffund
Ian Tietjen, Cole Schonhofer, Amanda Sciorillo, Maya E. Naidu, Zahra Haq, Toshitha Kannan, Andrew V. Kossenkov, Jocelyn Rivera, Karam Mounzer, Colin Hart, Kwasi Gyampoh, Zhe Yuan, Karren D. Beattie, Topul Rali, Kristy Shuda McGuire, Rohan A. Davis, Luis J. Montaner

Bibliographic record

VenueAntimicrobial Agents and Chemotherapy · 2023
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicBioactive Compounds and Antitumor Agents
Canadian institutionsSimon Fraser University
FundersNational Institute of Allergy and Infectious DiseasesAlliance for Accelerating Excellence in Science in AfricaAfrican Academy of SciencesBen Franklin Technology Partners of Northeastern PennsylvaniaCanadian Institutes of Health ResearchDepartment of Education and TrainingSimon Fraser UniversityWellcome TrustGriffith UniversityNew Partnership for Africa's DevelopmentAustralian Research CouncilPennsylvania Department of Community and Economic DevelopmentFred J. Brotherton Charitable FoundationChristian R. and Mary F. Lindback Foundation
KeywordsKinaseProtein kinase CSignal transductionHuman immunodeficiency virus (HIV)Transcription (linguistics)Transcription factorCancer researchBiologyChemistryVirologyCell biologyBiochemistryGene

Abstract

fetched live from OpenAlex

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (–)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.360
Threshold uncertainty score0.902

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.039
GPT teacher head0.340
Teacher spread0.301 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2023
Admission routes2
Has abstractyes

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